Synthesis and evaluation of aliphatic-chain hydroxamates capped with osthole derivatives as histone deacetylase inhibitors

Wei Jan Huang, Ching Chow Chen, Shi Wei Chao, Chia Chun Yu, Chen Yui Yang, Jih Hwa Guh, Yun Chieh Lin, Chiao I. Kuo, Ping Yang, Chung I. Chang

研究成果: 雜誌貢獻文章

25 引文 (Scopus)

摘要

Our previous studies have demonstrated that osthole, a Chinese herbal compound, could be incorporated into the hydroxycinnamide scaffold of LBH-589, a potent HDAC inhibitor, as an effective hydrophobic cap; the resulting compounds showed significant potency against several HDAC isoforms. Here, we presented a series of osthole derivatives fused with the aliphatic-hydroxamate core of suberoylanilide hydroxamic acid (SAHA), a clinically-approved HDAC inhibitor. Several compounds showed potent activity against nuclear HDACs. Further assays against individual HDAC isoforms revealed that some compounds showed not only SAHA-like activity towards HDAC1, -4 and -6, they inhibited HDAC8 by log difference than SAHA and thus exhibited a broader HDAC inhibition spectrum. Among them, compound 6g showed potent antiproliferative effect on several human cancer cell lines.

原文英語
頁(從 - 到)4042-4049
頁數8
期刊European Journal of Medicinal Chemistry
46
發行號9
DOIs
出版狀態已發佈 - 九月 2011

指紋

Histone Deacetylase Inhibitors
Derivatives
Protein Isoforms
Scaffolds
Assays
Cells
Cell Line
osthol
vorinostat
Neoplasms

ASJC Scopus subject areas

  • Drug Discovery
  • Organic Chemistry
  • Pharmacology

引用此文

Synthesis and evaluation of aliphatic-chain hydroxamates capped with osthole derivatives as histone deacetylase inhibitors. / Huang, Wei Jan; Chen, Ching Chow; Chao, Shi Wei; Yu, Chia Chun; Yang, Chen Yui; Guh, Jih Hwa; Lin, Yun Chieh; Kuo, Chiao I.; Yang, Ping; Chang, Chung I.

於: European Journal of Medicinal Chemistry, 卷 46, 編號 9, 09.2011, p. 4042-4049.

研究成果: 雜誌貢獻文章

Huang, Wei Jan ; Chen, Ching Chow ; Chao, Shi Wei ; Yu, Chia Chun ; Yang, Chen Yui ; Guh, Jih Hwa ; Lin, Yun Chieh ; Kuo, Chiao I. ; Yang, Ping ; Chang, Chung I. / Synthesis and evaluation of aliphatic-chain hydroxamates capped with osthole derivatives as histone deacetylase inhibitors. 於: European Journal of Medicinal Chemistry. 2011 ; 卷 46, 編號 9. 頁 4042-4049.
@article{d547cee3b3834931b916be1bbad3dba0,
title = "Synthesis and evaluation of aliphatic-chain hydroxamates capped with osthole derivatives as histone deacetylase inhibitors",
abstract = "Our previous studies have demonstrated that osthole, a Chinese herbal compound, could be incorporated into the hydroxycinnamide scaffold of LBH-589, a potent HDAC inhibitor, as an effective hydrophobic cap; the resulting compounds showed significant potency against several HDAC isoforms. Here, we presented a series of osthole derivatives fused with the aliphatic-hydroxamate core of suberoylanilide hydroxamic acid (SAHA), a clinically-approved HDAC inhibitor. Several compounds showed potent activity against nuclear HDACs. Further assays against individual HDAC isoforms revealed that some compounds showed not only SAHA-like activity towards HDAC1, -4 and -6, they inhibited HDAC8 by log difference than SAHA and thus exhibited a broader HDAC inhibition spectrum. Among them, compound 6g showed potent antiproliferative effect on several human cancer cell lines.",
keywords = "Histone deacetylase, LBH-589, Molecular modeling, Osthole, SAHA",
author = "Huang, {Wei Jan} and Chen, {Ching Chow} and Chao, {Shi Wei} and Yu, {Chia Chun} and Yang, {Chen Yui} and Guh, {Jih Hwa} and Lin, {Yun Chieh} and Kuo, {Chiao I.} and Ping Yang and Chang, {Chung I.}",
year = "2011",
month = "9",
doi = "10.1016/j.ejmech.2011.06.002",
language = "English",
volume = "46",
pages = "4042--4049",
journal = "European Journal of Medicinal Chemistry",
issn = "0223-5234",
publisher = "Elsevier Masson SAS",
number = "9",

}

TY - JOUR

T1 - Synthesis and evaluation of aliphatic-chain hydroxamates capped with osthole derivatives as histone deacetylase inhibitors

AU - Huang, Wei Jan

AU - Chen, Ching Chow

AU - Chao, Shi Wei

AU - Yu, Chia Chun

AU - Yang, Chen Yui

AU - Guh, Jih Hwa

AU - Lin, Yun Chieh

AU - Kuo, Chiao I.

AU - Yang, Ping

AU - Chang, Chung I.

PY - 2011/9

Y1 - 2011/9

N2 - Our previous studies have demonstrated that osthole, a Chinese herbal compound, could be incorporated into the hydroxycinnamide scaffold of LBH-589, a potent HDAC inhibitor, as an effective hydrophobic cap; the resulting compounds showed significant potency against several HDAC isoforms. Here, we presented a series of osthole derivatives fused with the aliphatic-hydroxamate core of suberoylanilide hydroxamic acid (SAHA), a clinically-approved HDAC inhibitor. Several compounds showed potent activity against nuclear HDACs. Further assays against individual HDAC isoforms revealed that some compounds showed not only SAHA-like activity towards HDAC1, -4 and -6, they inhibited HDAC8 by log difference than SAHA and thus exhibited a broader HDAC inhibition spectrum. Among them, compound 6g showed potent antiproliferative effect on several human cancer cell lines.

AB - Our previous studies have demonstrated that osthole, a Chinese herbal compound, could be incorporated into the hydroxycinnamide scaffold of LBH-589, a potent HDAC inhibitor, as an effective hydrophobic cap; the resulting compounds showed significant potency against several HDAC isoforms. Here, we presented a series of osthole derivatives fused with the aliphatic-hydroxamate core of suberoylanilide hydroxamic acid (SAHA), a clinically-approved HDAC inhibitor. Several compounds showed potent activity against nuclear HDACs. Further assays against individual HDAC isoforms revealed that some compounds showed not only SAHA-like activity towards HDAC1, -4 and -6, they inhibited HDAC8 by log difference than SAHA and thus exhibited a broader HDAC inhibition spectrum. Among them, compound 6g showed potent antiproliferative effect on several human cancer cell lines.

KW - Histone deacetylase

KW - LBH-589

KW - Molecular modeling

KW - Osthole

KW - SAHA

UR - http://www.scopus.com/inward/record.url?scp=80052934367&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=80052934367&partnerID=8YFLogxK

U2 - 10.1016/j.ejmech.2011.06.002

DO - 10.1016/j.ejmech.2011.06.002

M3 - Article

C2 - 21712146

AN - SCOPUS:80052934367

VL - 46

SP - 4042

EP - 4049

JO - European Journal of Medicinal Chemistry

JF - European Journal of Medicinal Chemistry

SN - 0223-5234

IS - 9

ER -